施貴寶 (BMY) 2021 Q3 法說會逐字稿

Good day, and welcome to the Bristol-Myers Squibb 2021 Third Quarter Results Conference Call. Today's conference is being recorded. At this time, I would like to turn the conference over to Mr. Tim Power, Vice President, Investor Relations. Please go ahead, sir.

美好的一天，歡迎參加百時美施貴寶 2021 年第三季度業績電話會議。今天的會議正在錄製中。現在，我想將會議交給投資者關係副總裁 Tim Power 先生。請繼續，先生。

Thanks, Christina, and good morning, everyone. Thanks for joining us for our third quarter 2021 earnings call. Joining me this morning with prepared remarks are Giovanni Caforio, our Board Chair and Chief Executive Officer; and David Elkins, our Chief Financial Officer. Also, with me for today's call are Chris Boerner, our Chief Commercialization Officer; and Samit Hirawat, our Chief Medical Officer and Head of Global Drug Development.

謝謝克里斯蒂娜，大家早上好。感謝您參加我們的 2021 年第三季度財報電話會議。今天早上與我一起發表準備好的講話的是我們的董事會主席兼首席執行官喬瓦尼·卡福里奧 (Giovanni Caforio)；和我們的首席財務官大衛埃爾金斯。此外，與我一起參加今天電話會議的還有我們的首席商業化官 Chris Boerner；以及我們的首席醫療官兼全球藥物開發主管 Samit Hirawat。

You'll note that we posted slides to bms.com and you can use those to follow along with David and Giovanni's remarks. But before we get started, I'll read our forward-looking statements. During today's call, we'll make statements about the company's future plans and prospects that constitute forward-looking statements. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the company's SEC filings. These forward-looking statements represent our estimates as of today and should not be relied upon as representing our estimates as of any future date. We specifically disclaim any obligation to update forward-looking statements even if our estimates change.

您會注意到我們已將幻燈片發佈到 bms.com，您可以使用這些幻燈片來了解 David 和 Giovanni 的評論。但在我們開始之前，我將閱讀我們的前瞻性聲明。在今天的電話會議中，我們將就公司的未來計劃和前景發表前瞻性聲明。由於各種重要因素（包括公司提交給美國證券交易委員會的文件中討論的因素），實際結果可能與這些前瞻性陳述所示的結果存在重大差異。這些前瞻性陳述代表了我們截至目前的估計，不應被視為代表我們截至未來任何日期的估計。即使我們的估計發生變化，我們特別不承擔更新前瞻性陳述的義務。

We'll also focus our comments on our non-GAAP financial measures, which are adjusted to exclude certain specified items. Reconciliations of these non-GAAP financial measures to the most comparable GAAP measures are available at bms.com.

我們還將重點關注我們的非公認會計準則財務指標，這些指標經過調整以排除某些特定項目。這些非 GAAP 財務指標與最具可比性的 GAAP 指標的調節表可在 bms.com 上找到。

And with that, I'll hand it over to Giovanni.

這樣，我就把它交給喬瓦尼了。

Thank you, Tim, and good morning, everyone. I hope that you're all doing well. Now turning to Slide 4. I'm pleased to report a very good third quarter with solid secular growth driven by strong commercial execution and good progress in our pipeline. I'm proud of the performance of our commercial teams who drove demand growth for our launch products and delivered solid performance of our inline products, including Revlimid, Opdivo and Eliquis.

謝謝蒂姆，大家早上好。我希望你們一切都好。現在轉向幻燈片 4。我很高興地報告第三季度的業績非常好，在強大的商業執行力和我們的管道進展良好的推動下，實現了穩健的長期增長。我為我們商業團隊的表現感到自豪，他們推動了我們上市產品的需求增長，並為我們的內嵌產品（包括 Revlimid、Opdivo 和 Eliquis）提供了穩定的性能。

In R&D, we are progressing the most promising assets in our pipeline for sustained growth. In the quarter, we advanced our third I-O mechanism with a fixed dose of relatlimab plus nivo accepted for priority review in the U.S. for the treatment of patients with unresectable or metastatic melanoma. This is an important development for the I-O franchise, and we have additional data readouts for Opdivo on the horizon.

在研發方面，我們正在開發管道中最有前途的資產，以實現持續增長。本季度，我們推進了第三個 I-O 機制，固定劑量的 relatlimab 加 nivo 已在美國接受優先審查，用於治療不可切除或轉移性黑色素瘤患者。這是 I-O 特許經營權的一項重要發展，我們即將獲得 Opdivo 的更多數據讀數。

From a financial perspective, we reported sales of $11.6 billion and non-GAAP EPS of $2 with growth of 10% and 23%, respectively. I'm encouraged by our results and how they position us for the rest of '21 and for the future. As a result, we are reaffirming our revenue guidance and raising the lower end of our non-GAAP EPS guidance range.

從財務角度來看，我們的銷售額為 116 億美元，非 GAAP 每股收益為 2 美元，分別增長 10% 和 23%。我對我們的成果以及它們如何為我們 21 年剩餘時間和未來的定位感到鼓舞。因此，我們重申了我們的收入指引，並提高了非公認會計準則每股收益指引範圍的下限。

Our balance sheet is strong, and we continue to pursue a disciplined capital allocation strategy focused on investing in internal and external innovation opportunities.

我們的資產負債表強勁，我們繼續奉行嚴格的資本配置策略，重點投資於內部和外部創新機會。

On the IP front, we are pleased with the decision by the U.S. Court of Appeals for the Federal Circuit upholding the Eliquis IP and providing exclusivity until 2028 under existing settlements. This decision confirms our belief in the value of the science behind Eliquis and the underlying IP protecting its innovation. Overall, I'm extremely pleased with our progress in the quarter.

在知識產權方面，我們對美國聯邦巡迴上訴法院維持 Eliquis 知識產權並根據現有和解提供 2028 年之前的排他性的決定感到高興。這一決定證實了我們對 Eliquis 背後的科學價值以及保護其創新的基礎知識產權的信念。總的來說，我對本季度的進展非常滿意。

Turning to our execution scorecard on Slide 5. At the start of the year, I laid out this scorecard with the milestones we thought would be important for us to deliver in order to successfully renew our portfolio. The team has worked hard, and I'm proud that we're making progress across the board. A number of accomplishments were included on the prior slide, so I won't go through all the details, but I want to call out a few highlights here. David will provide more details in his remarks.

轉向幻燈片 5 上的執行記分卡。年初，我列出了這張記分卡，其中列出了我們認為對我們成功更新我們的投資組合至關重要的里程碑。該團隊一直在努力工作，我為我們在各方面取得的進步感到自豪。上一張幻燈片中包含了許多成就，因此我不會詳細介紹所有細節，但我想在此指出一些亮點。大衛將在講話中提供更多細節。

I'll start with deucravacitinib. Deucrava has demonstrated a compelling and differentiated profile in 2 Phase III studies as the oral treatment of choice in psoriasis and is an important asset with significant potential across a number of indications, including psoriatic arthritis, where we have already initiated a Phase III program. Although we did not achieve proof-of-concept in a Phase II study for ulcerative colitis, we are committed to advancing our promising deucravacitinib clinical program in inflammatory bowel disease, including another study for ulcerative colitis as well as Crohn's disease in lupus and other immune-mediated diseases.

我將從 deucravacitinib 開始。 Deucrava 在兩項 III 期研究中證明了作為銀屑病首選口服治療藥物的引人注目和差異化特徵，並且是一項重要資產，在許多適應症（包括銀屑病關節炎）方面具有巨大潛力，我們已經啟動了一項 III 期計劃。儘管我們沒有在潰瘍性結腸炎的 II 期研究中實現概念驗證，但我們致力於推進我們在炎症性腸病方面有前途的 deucravacitinib 臨床計劃，包括另一項針對潰瘍性結腸炎以及狼瘡和其他免疫性疾病的克羅恩病的研究介導的疾病。

We continue to make great progress in our cell therapy franchise, and we look forward to presenting the transform data for Breyanzi in second-line DLBCL at ASH. We're excited with the strength of this data, which have the potential to enable our cell therapy franchise to reach a broader set of patients.

我們的細胞治療系列繼續取得巨大進展，我們期待在 ASH 上展示 Breyanzi 在二線 DLBCL 中的轉化數據。我們對這些數據的強度感到興奮，這些數據有可能使我們的細胞療法專營權惠及更廣泛的患者。

And we are also looking forward to presenting data from the first Phase II study for Milvexian for VTE prevention in patients undergoing total knee replacement at the American Heart Association conference in a few weeks. Looking at the overall strength of execution so far, I am confident that we are on track to deliver what is required for us to renew our portfolio.

我們還期待在幾週後的美國心臟協會會議上展示 Milvexian 用於預防全膝關節置換術患者 VTE 的第一項 II 期研究的數據。縱觀迄今為止的整體執行力度，我相信我們有望實現更新投資組合所需的目標。

Moving to Slide 6. It has been 2 years since we formed the new Bristol-Myers Squibb. As I reflect on this time, we have already made great progress. We are doing what we set out to do: delivering on the value drivers of the integration, and most importantly, establishing a strong foundation for our company's growth well into the future.

轉到幻燈片 6。我們成立新的百時美施貴寶已經過去兩年了。現在回想起來，我們已經取得了很大的進步。我們正在做我們打算做的事情：提供整合的價值驅動力，最重要的是，為我們公司未來的發展奠定堅實的基礎。

Knowing that we face losses of exclusivity in the coming years, I recognize executing well on our multiple launches and continuing to advance our pipeline is particularly important for us. When I reflect on the last 2 years, I'm pleased on both fronts. We see strong demand for our newly launched products, and we are delivering on the promise of our pipeline, including a broadening data set for our launch products and continuing progress with our next generation of assets, such as Milvexian and iberdomide.

知道我們在未來幾年將面臨獨家經營權的喪失，我認識到在我們的多次發布中表現良好並繼續推進我們的產品線對我們來說尤為重要。當我回顧過去兩年時，我在這兩方面都感到高興。我們看到對我們新推出的產品的強勁需求，並且我們正在兌現我們的管道承諾，包括擴大我們推出產品的數據集以及我們下一代資產（例如 Milvexian 和 iberdomide）的持續進展。

Our company today is more diversified than ever before with 4 durable franchises and the financial flexibility to continue to invest in innovation. As we recently announced, we will be hosting an investor event on November 16 in New York City to review our progress over the last 2 years and further discuss the company's strategy, pipeline and business opportunities. I look forward to the meeting, and I hope you will join us.

今天，我們的公司比以往任何時候都更加多元化，擁有 4 個持久的特許經營權以及繼續投資創新的財務靈活性。正如我們最近宣布的，我們將於 11 月 16 日在紐約舉辦投資者活動，回顧過去兩年的進展，並進一步討論公司的戰略、管道和商業機會。我期待著這次會議，並希望您能加入我們。

In closing, we have made significant progress through this period, and I would like to thank our global teams who have maintained the focus on delivering for patients.

最後，我們在這一時期取得了重大進展，我要感謝我們的全球團隊，他們一直專注於為患者提供服務。

With that, I'll turn it over to David to walk you through the financials. David?

接下來，我將把它交給 David，讓他帶您了解財務狀況。大衛？

Thank you, Giovanni, and thank you all for joining our call today. Starting with our top line performance on Slide 8. We had yet another strong quarter with third quarter revenues growing double digits versus prior year, primarily due to demand -- increased demand for our inline brands, but as well as our new product portfolio. So let me shed some light on some of our product performance, starting with Eliquis on Slide 9.

謝謝喬瓦尼，也感謝大家今天加入我們的電話會議。從幻燈片 8 上我們的營收表現開始。我們又一個強勁的季度，第三季度收入比去年同期增長了兩位數，這主要是由於需求——對我們的內聯品牌以及我們的新產品組合的需求增加。讓我從幻燈片 9 上的 Eliquis 開始，介紹一下我們的一些產品性能。

Eliquis continues to perform very strongly with global sales up 15% versus prior year. In the U.S., sales grew 18% versus prior year. Demand growth continues to be strong with total prescription growth of 14% versus last year, driven by OAC products' market share gains and growth in new-to-brand volumes. Sequentially, as usual, sales were impacted by the expected coverage gap liability that occurs in the third and fourth quarters each year. We expect strong new-to-brand share growth to further translate to overall total prescription growth. Internationally, sales grew 12% versus prior year, primarily due to demand. Shares continue to increase across all key geographies and continues to rank as the #1 OAC in multiple markets with additional room to grow. We remain really pleased with Eliquis' execution around the world and expect to continue to grow Eliquis' share within a growing class.

Eliquis 繼續表現強勁，全球銷售額比去年增長 15%。在美國，銷售額比上年增長 18%。受 OAC 產品市場份額增長和新品牌銷量增長的推動，需求增長持續強勁，總處方量較去年增長 14%。因此，與往常一樣，銷售受到每年第三和第四季度發生的預期承保缺口負債的影響。我們預計新品牌份額的強勁增長將進一步轉化為總體處方增長。在國際範圍內，銷售額比上年增長 12%，這主要是由於需求。所有主要地區的股價持續上漲，並繼續在多個市場中排名第一的 OAC，並具有額外的增長空間。我們對 Eliquis 在全球的執行情況仍然非常滿意，並期望在不斷增長的類別中繼續增加 Eliquis 的份額。

Now moving to Opdivo's performance on Slide 10. We are pleased with the continued momentum for the brand, with sales growth of 7% versus prior year. In the U.S., sales grew 4% versus last year, primarily driven by uptake in first-line lung cancer and our multiple other new launches this year. And sequentially, we had demand growth of 5%, which was offset by a work down of $40 million in inventory build we noted in the second quarter.

現在轉向幻燈片 10 中 Opdivo 的表現。我們對該品牌的持續增長勢頭感到滿意，銷售額比去年增長了 7%。在美國，銷售額比去年增長了 4%，這主要是由於一線肺癌藥物的使用以及我們今年推出的多個其他新產品的推動。隨後，我們的需求增長了 5%，但我們在第二季度注意到庫存建設減少了 4000 萬美元，從而抵消了這一增長。

Our commercial teams continue to execute well. We've retained strong positions in core indications such as melanoma and renal and are very pleased with the performance of our newer indications.

我們的商業團隊繼續表現良好。我們在黑色素瘤和腎臟等核心適應症方面保持了強勢地位，並對我們新適應症的表現感到非常滿意。

Outside the U.S., we had another strong quarter with sales up 11% versus last year. Growth was primarily driven by demand for new indications that expanded access in Latin America, Turkey and Russia. We continue to see strong uptake from our new launches in lung and renal cancer in Germany and Japan with pricing and reimbursement discussions ongoing in other key markets. These launches, together with recent approvals of first-line gastric and adjuvant esophageal cancer, are expected to contribute to further growth internationally.

在美國以外的地區，我們又經歷了一個強勁的季度，銷售額比去年增長了 11%。增長主要是由對新適應症的需求推動的，這些新適應症擴大了拉丁美洲、土耳其和俄羅斯的准入範圍。我們繼續看到我們在德國和日本推出的肺癌和腎癌新藥的市場份額強勁，其他主要市場正在進行定價和報銷討論。這些產品的上市，加上最近批准的一線胃癌和輔助食管癌藥物，預計將有助於國際上的進一步增長。

Based on positive momentum from our current launches and future potential launches, including first-line esophageal in May of next year as well as expansion opportunities from clinical trials that will read out over the next few years, the promise for Opdivo's continued growth is high.

基於我們當前推出的產品和未來潛在推出的積極勢頭，包括明年 5 月的一線食管治療，以及未來幾年臨床試驗的擴展機會，Opdivo 持續增長的前景很高。

Turning to our inline multiple myeloma portfolio on Slide 11. Revlimid was up 11% globally, primarily driven by demand for triple-based therapies and increasing treatment duration. Pomalyst global sales were up 10%, driven by continued demand for triple-based therapies and use in earlier lines.

轉向幻燈片 11 上我們的內聯多發性骨髓瘤產品組合。來那度胺在全球範圍內上漲了 11%，這主要是由於對三聯療法的需求和治療持續時間的延長所推動的。由於對三聯療法的持續需求以及早期產品線的使用，Pomalyst 全球銷售額增長了 10%。

Now moving to our new products on Slide 12. We continue to be very pleased with our new products, which generated sales of $344 million in the third quarter. This new diversified portfolio is already annualizing close to $1.5 billion run rate, giving us great confidence that we are on our way to renewing our business with products that are much earlier in their life cycle.

現在轉到幻燈片 12 上的新產品。我們仍然對我們的新產品感到非常滿意，該產品在第三季度創造了 3.44 億美元的銷售額。這個新的多元化投資組合的年化運行率已接近 15 億美元，這讓我們充滿信心，我們正在利用處於生命週期早期的產品來更新我們的業務。

So let's start with Reblozyl, which generated strong sales of $160 million in the third quarter, up 67% versus prior year. Sales growth in the U.S. was primarily driven by continued demand in the ESA refractory MDS patients as well as a $20 million to $25 million inventory build. We are very encouraged by the recent NCCN Guideline update that now recommends evaluating ESA response sooner at 6 to 8 weeks instead of the previously recommended 12 to 16 weeks. This supports the need to monitor and potentially treat new patients earlier in their treatment journey. Additionally, we remain focused on ensuring we receive the most appropriate dose for sustained benefit.

讓我們從 Reblozyl 開始，該產品第三季度銷售額強勁，達到 1.6 億美元，比去年同期增長 67%。美國的銷售增長主要是由 ESA 難治性 MDS 患者的持續需求以及 2000 萬至 2500 萬美元的庫存建設推動的。我們對最近的 NCCN 指南更新感到非常鼓舞，該指南現在建議儘早在 6 至 8 週內評估 ESA 的響應，而不是之前建議的 12 至 16 週。這支持了在治療過程的早期監測和潛在治療新患者的需要。此外，我們仍然致力於確保我們獲得最合適的劑量以獲得持續的益處。

Outside the U.S., uptake continues to be strong in countries where Reblozyl was launched. Sales were impacted by the usual price review 1 year after launch in Germany. We expect to launch in Italy and the Netherlands in Q4 pending reimbursement discussions and in more countries in 2022 to drive additional growth for the brand.

在美國以外的地區，Reblozyl 上市國家的採用率仍然強勁。在德國推出一年後，銷售受到了通常價格審查的影響。我們預計將於第四季度在意大利和荷蘭推出，等待報銷討論，並於 2022 年在更多國家推出，以推動該品牌的進一步增長。

Moving to our cell therapies Abecma and Breyanzi. Demand for Abecma, our first-in-class BCMA CAR T remains robust. We generated $71 million in the third quarter versus $24 million in the second quarter. Remember that 2Q revenues consisted of only 1.5 months of sales having launched in mid-May, so performance this quarter reflects a full quarter of sales. Demand continues to exceed supply, and we expect Q4 revenues to be largely similar to Q3.

轉向我們的細胞療法 Abecma 和 Breyanzi。對我們一流的 BCMA CAR T Abecma 的需求仍然強勁。我們第三季度的營收為 7100 萬美元，而第二季度為 2400 萬美元。請記住，第二季度收入僅包括 5 月中旬推出的 1.5 個月的銷售，因此本季度的業績反映了整個季度的銷售。需求繼續超過供應，我們預計第四季度收入將與第三季度基本相似。

Now moving to our CD19 CAR T, Breyanzi. Sales in the quarter were $30 million versus $17 million in the prior quarter. Sales increased due to patient demand with physicians recognizing Breyanzi's best-in-class profile. We're extremely pleased to have clinically meaningful EFS data in second-line large B-cell lymphoma and look forward to presenting the data at ASH and bringing this treatment to earlier line patients in 2022.

現在轉向我們的 CD19 CAR T，Breyanzi。本季度銷售額為 3000 萬美元，上一季度銷售額為 1700 萬美元。由於患者的需求以及醫生認可 Breyanzi 一流的形象，銷售額有所增加。我們非常高興在二線大 B 細胞淋巴瘤中獲得具有臨床意義的 EFS 數據，並期待在 ASH 上展示這些數據，並於 2022 年將這種治療方法帶給早期患者。

Turning to Zeposia. Global revenues were $40 million in the quarter, driven by multiple sclerosis launch and onetime inventory build in the U.S. The MS launch continues to progress well, where Zeposia remains the S1P of choice in terms of written prescriptions. We continue to focus on establishing Zeposia as not only the S1P of choice, but also the oral treatment of choice in MS. Our launch in UC is also progressing well in the U.S. We are encouraged by the initial uptake and growth in the number of new trialists since launch in June. Our focus is building on volume, establishing demand for this oral biologic-like medicine, while broadening access over time.

轉向澤波西婭。本季度全球收入為 4000 萬美元，主要得益於多發性硬化症藥物的上市和美國一次性庫存的增加。MS 的上市繼續進展順利，Zeposia 仍然是書面處方方面的 S1P 首選。我們繼續致力於將 Zeposia 打造為不僅是首選的 S1P，而且是 MS 的首選口服治療藥物。我們在 UC 的推出在美國也進展順利。自 6 月份推出以來，新試用者數量的初步吸收和增長令我們感到鼓舞。我們的重點是擴大產量，建立對這種口服生物類藥物的需求，同時隨著時間的推移擴大獲取範圍。

We are also very pleased to have just received CHMP positive opinion in Europe and look forward to making Zeposia available to patients living with UC as soon as possible.

我們也很高興剛剛在歐洲收到 CHMP 的積極意見，並期待盡快為 UC 患者提供 Zeposia。

Lastly, we're making progress on establishing Onureg in first-line maintenance in AML patients. Onureg generated sales of $21 million in the quarter, primarily driven by increased demand as well as inventory build versus prior quarter. We continue to focus on shaping the new maintenance segment and increasing adoption and patient adherence.

最後，我們在將 Onureg 用於 AML 患者一線維持治療方面取得了進展。 Onureg 本季度銷售額為 2100 萬美元，主要是由於需求增加以及與上一季度相比庫存增加所致。我們繼續專注於塑造新的維護領域並提高采用率和患者依從性。

Now let's turn our attention over to P&L on Slide 13. We've already covered our strong sales for the quarter, so let me walk you through a few other non-GAAP key line items. Gross margin increased versus prior year, primarily due to lower royalty payments. Operating expenses were higher than last year, particularly in R&D due to COVID recovery, but also slightly in MS&A due to investments supporting our launch and prelaunch activities. MS&A versus prior quarter did experience some softness due to timing of investments that have shifted to the fourth quarter. Our effective tax rate of 14.9% was primarily driven by earnings mix. Overall, non-GAAP EPS increased 23% year-over-year.

現在讓我們將注意力轉向幻燈片 13 上的損益表。我們已經介紹了本季度的強勁銷售情況，所以讓我帶您了解其他一些非 GAAP 關鍵項目。毛利率較上年有所增加，主要是由於特許權使用費減少。運營費用高於去年，特別是由於新冠疫情復甦導致的研發費用，但由於支持我們的發布和預發布活動的投資，管理與管理費用也略有上升。由於投資時間已轉移至第四季度，MS&A 與上一季度相比確實出現了一些疲軟。我們 14.9% 的有效稅率主要是由盈利組合推動的。總體而言，非 GAAP 每股收益同比增長 23%。

Now moving to our balance sheet and capital allocation on Slide 14. Our liquidity position remains strong with almost $16 billion in cash and marketable securities and a strong cash flow from operations of $5.3 billion in the quarter. Our capital allocation priorities remain unchanged. We have significant financial flexibility to support a balanced approach to capital allocation. Our priorities are to continue to renew and diversify our portfolio through business development, paying down our debt and returning capital to shareholders. We have executed several business development deals this year, bringing in differentiated early-stage assets. Business development remains a top priority as a leading innovation-based company.

現在轉向幻燈片 14 上的資產負債表和資本配置。我們的流動性狀況依然強勁，擁有近 160 億美元的現金和有價證券，本季度運營產生的現金流強勁，達 53 億美元。我們的資本配置重點保持不變。我們擁有巨大的財務靈活性來支持平衡的資本配置方法。我們的首要任務是通過業務發展、償還債務和向股東返還資本來繼續更新我們的投資組合併使其多元化。今年我們執行了多項業務開發交易，引入了差異化的早期資產。作為一家領先的創新型公司，業務發展仍然是重中之重。

We have paid down $6 billion in debt year-to-date and are committed to maintaining our strong investment-grade rating. As it relates to returning capital to shareholders, we're committed to growing our dividend subject to Board approval, and remain opportunistic about share repurchases. We have already purchased $3.5 billion of shares to date, and we currently have approximately $3 billion remaining in our authorization program.

今年迄今為止，我們已償還了 60 億美元的債務，並致力於維持我們強勁的投資級評級。由於這關係到向股東返還資本，我們致力於在董事會批准的情況下增加股息，並對股票回購保持機會態度。迄今為止，我們已經購買了 35 億美元的股票，目前我們的授權計劃還剩大約 30 億美元。

Now turning to our guidance on Slide 15. Based on the strong performance in the quarter, we are reaffirming full year sales and raising the lower end of our non-GAAP EPS guidance. We continue to expect revenues to increase at the higher end of our guidance and gross margin to be approximately 80%.

現在轉向我們對幻燈片 15 的指導。基於本季度的強勁表現，我們重申全年銷售額並提高非 GAAP 每股收益指導的下限。我們繼續預計收入將在我們指導的高端增加，毛利率將達到 80% 左右。

Moving to operating expenses. We are maintaining our MS&A and R&D guidance for the year. As I mentioned earlier, MS&A, we are expecting higher expenses in the fourth quarter due to timing of investments that shifted by a quarter. Additionally, we're updating our tax rate guidance to approximately 16.5%, primarily due to earnings mix.

轉向運營費用。我們維持今年的管理、分析和研髮指導。正如我之前提到的，由於投資時間發生了一個季度的變化，我們預計第四季度的支出將會增加。此外，我們將稅率指導值更新為約 16.5%，這主要是由於收入組合的原因。

All in all, I'm pleased with our performance. We had another remarkable quarter for the company and continue to execute well against our plans and to diversify and renew our portfolio. This performance couldn't have been achieved without the passion and dedication of our employees around the world, and I look forward to providing you future updates on our progress.

總而言之，我對我們的表現感到滿意。我們公司又度過了一個非凡的季度，並繼續出色地執行我們的計劃，並實現我們的投資組合多元化和更新。如果沒有我們世界各地員工的熱情和奉獻精神，就不可能取得這樣的業績，我期待著向您提供有關我們進展的最新信息。

With that, I'll now turn it back over to Tim and Giovanni for Q&A.

現在，我將把它轉回蒂姆和喬瓦尼進行問答。

Thanks, David. Christina, could we go to our first question, please?

謝謝，大衛。克里斯蒂娜，我們可以回答第一個問題嗎？

(Operator Instructions)

（操作員說明）

We'll take our first question from Geoff Meacham with Bank of America.

我們將回答美國銀行傑夫·米查姆 (Geoff Meacham) 提出的第一個問題。

Congrats on a good quarter. I just wanted to ask on the new launches, the Abecma launch was pretty good. Just give us a sense for how much of that is still a bolus of patients versus underlying demand? And just also help us with the impact that you're still seeing from the viral vector manufacturing. And then the second question, just on Opdivo. It was flat sequentially, and how do you view going into 2022 with respect to what indications could be more of a tipping point versus others?

祝賀季度表現良好。我只是想問一下新發布的情況，Abecma 的發布非常好。讓我們了解一下，與潛在需求相比，其中有多少仍然是大量患者？並且還可以幫助我們解決您仍然從病毒載體製造中看到的影響。然後是第二個問題，關於 Opdivo。環比持平，您如何看待進入 2022 年時哪些跡象可能比其他跡象更能成為轉折點？

Thank you, Geoff. Thanks for the questions. This is Giovanni. Let me just start with a couple of comments, and then I'll ask Chris to answer both of your questions. I just wanted to step back and really think about cell therapy. And you'll remember, in the past, we've had a number of discussions about whether cell therapy treatments would have a fast uptake in the marketplace where this market would grow over time. There were concerns with payers' willingness to provide coverage for those therapies.

謝謝你，傑夫。感謝您的提問。這是喬瓦尼。讓我首先發表一些評論，然後我將請克里斯回答你們的兩個問題。我只是想退後一步，認真思考細胞療法。您會記得，在過去，我們已經就細胞療法是否會在市場上快速普及進行了多次討論，並且該市場會隨著時間的推移而增長。人們擔心付款人是否願意為這些療法提供保險。

And I must say, when I look at the experience that we've had with both Abecma and Breyanzi, it really confirms our belief that given the right treatments with the right efficacy and safety profile, there is tremendous willingness of physicians to prescribe and drive increased adoption in the marketplace. Many of the payer dynamics have been resolved. So beyond, obviously, the question that Chris will answer, as we look at the medium and the long term and the commitment we've made to our broad cell therapy portfolio, I'm very reassured that the commercial potential of this modality is being recognized, I would say, significantly more than in the past. Chris?

我必須說，當我看到我們在 Abecma 和 Breyanzi 方面的經驗時，它確實證實了我們的信念，即給予具有正確療效和安全性的正確治療方法，醫生非常願意開處方和駕駛市場採用率提高。許多付款人動態已經得到解決。因此，顯然，除了克里斯將回答的問題之外，當我們著眼於中期和長期以及我們對廣泛的細胞治療產品組合做出的承諾時，我非常放心，這種模式的商業潛力正在發揮作用。我想說，人們的認識比過去要多得多。克里斯？

So thanks for the questions, Geoff. Let me start with cell therapy. So we are very pleased with the performance really of both Abecma and Breyanzi in the quarter. We saw a very nice increase in demand for both products. There was some bolus for Abecma still reflected in these numbers. But the underlying demand for that product looks very strong. The same is true with Breyanzi. We're very happy with the commercial execution for both of these products. We now have over 70 accounts that have been activated across both products. And the majority of those accounts have been or planned to imminently use one or both of the cell therapy products. So overall, I would say the commercial performance continues to be very good.

謝謝你的提問，傑夫。讓我從細胞療法開始。因此，我們對 Abecma 和 Breyanzi 在本季度的表現非常滿意。我們看到這兩種產品的需求都出現了非常好的增長。這些數字中仍然反映出 Abecma 的一些丸劑。但對該產品的潛在需求看起來非常強勁。布雷揚齊也是如此。我們對這兩種產品的商業執行感到非常滿意。目前，我們已在這兩種產品中激活了 70 多個帳戶。這些賬戶中的大多數已經或計劃立即使用一種或兩種細胞治療產品。總的來說，我想說商業表現仍然非常好。

As has been mentioned already, we're actively managing the supply constraints. Those mainly are impacting Abecma. And as David mentioned in his remarks, we do anticipate that Abecma sales in the fourth quarter are going to be roughly similar to what we saw in the third quarter. And we're, of course, continuing to stay very focused on managing through the vector supply constraints. And anticipate it being in a much better position on that front as we get into the second half of next year. But again, stepping back, as Giovanni just mentioned, we are very happy with what we're seeing in the marketplace on cell therapy and it confirms the opportunity we have to build a strong position here.

正如已經提到的，我們正在積極管理供應限制。這些主要影響的是 Abecma。正如 David 在講話中提到的那樣，我們確實預計 Abecma 第四季度的銷售額將與我們在第三季度看到的大致相似。當然，我們將繼續非常專注於克服載體供應限制。預計當我們進入明年下半年時，它在這方面會處於更好的位置。但話又說回來，正如喬瓦尼剛才提到的，我們對細胞治療市場上所看到的情況感到非常滿意，這證實了我們有機會在這裡建立強大的地位。

With respect to Opdivo, the performance for the quarter for I-O was really in line with expectations. We saw very strong double-digit growth relative to the same time last year. And while sales were flat, as you know, from Q2 into Q3, that was, as David mentioned, a function of inventory dynamics coming out of the second quarter. What is important here is that we had very solid growth in the quarter. We had solid growth relative to same time last year and quarter-over-quarter. And that growth was in the key tumors that are going to drive near and medium-term growth for the I-O franchise, notably in gastric cancer where we've seen a nice uptick since the approval in April.

就 Opdivo 而言，I-O 本季度的表現確實符合預期。與去年同期相比，我們看到了非常強勁的兩位數增長。正如您所知，雖然從第二季度到第三季度銷售額持平，但正如大衛提到的那樣，這是第二季度庫存動態的函數。重要的是我們在本季度實現了非常穩健的增長。與去年同期和環比相比，我們實現了穩健的增長。這種增長發生在關鍵腫瘤中，這些腫瘤將推動 I-O 特許經營權的近期和中期增長，特別是胃癌，自 4 月份批准以來，我們看到了胃癌的良好增長。

In renal cell cancer, we continue to see very strong demand. And we've seen coming at the end of the quarter some nice growth in first-line lung cancer. So overall, if you step back, we were very confident not only in the continued growth for Opdivo this year, but importantly, the momentum going into '22.

在腎細胞癌方面，我們繼續看到非常強勁的需求。我們已經看到，到本季度末，一線肺癌治療將出現一些良好的增長。因此，總的來說，如果退一步看，我們不僅對 Opdivo 今年的持續增長充滿信心，而且更重要的是，對進入 22 年的勢頭充滿信心。

We'll take our next question from Seamus Fernandez with Guggenheim.

我們將回答古根海姆謝默斯·費爾南德斯提出的下一個問題。

So first one is on deucravacitinib. Just wanted to get a little bit of a better sense. It just seems -- I was surprised to see that we don't have deucravacitinib listed as filed yet. I just don't know what the limitations are. Are there new data being added or that you plan to be added? Or is it just simply waiting for FDA's acceptance of the filing?

第一個是 deucravacitinib。只是想獲得一點更好的感覺。看起來——我很驚訝地發現我們還沒有列出已提交的 deucravacitinib。我只是不知道有什麼限制。是否正在添加新數據或您計劃添加新數據？還是只是等待FDA接受備案？

The second question really is as we think about the opportunity for deucravacitinib, I wanted to just get a better understanding of what Bristol believes is necessary to succeed in ulcerative colitis. It's our understanding that the IC90 may, in fact, be the most critical part of the development plan. And that perhaps deucravacitinib may not achieve that unless the dose is really pushed. And so just wondering if a long-acting formulation may be something that Bristol is pursuing. And then just a final question very quickly. Between your -- the MK2 inhibitor, the BTK inhibitor, the S1P1 that you have in Phase II. Would you call out any of these as having data in 2022 that we's should be watching for?

第二個問題實際上是，當我們考慮 deucravacitinib 的機會時，我想更好地了解布里斯托爾認為成功治療潰瘍性結腸炎的必要條件。據我們了解，IC90 實際上可能是開發計劃中最關鍵的部分。除非確實加大劑量，否則 deucravacitinib 可能無法實現這一目標。因此，我想知道布里斯托爾是否正在追求一種長效配方。然後很快就提出最後一個問題。在第二階段的 MK2 抑製劑、BTK 抑製劑和 S1P1 之間。您是否認為其中任何一個在 2022 年都有值得我們關注的數據？

Thank you, Seamus. Let me ask Samit to answer your questions.

謝謝你，西莫。讓我請薩米特回答你的問題。

Seamus, thank you for your questions. On the first one on deucrava, let me just first start by reiterating our confidence in the data which differentiates it and establishes it as a potential best oral therapy of choice in the future for patients with psoriasis. In terms of the filing, as you very well know, we don't comment on when we file but we certainly do make it public when the file has been accepted, validated after we have filed for the indication. So we will certainly make you aware and everyone aware when we hear as time goes. But having said that, we do anticipate bringing the medicine to patients in the second half of 2022, as we have said before.

西莫，謝謝你的提問。關於 deucrava 的第一個問題，首先讓我重申我們對數據的信心，這些數據使其與眾不同，並將其確立為銀屑病患者未來潛在的最佳口服療法選擇。就備案而言，正如您所知，我們不會評論何時提交，但我們肯定會在文件被接受時公開，並在我們提交指示後進行驗證。因此，隨著時間的推移，當我們聽到這一消息時，我們一定會讓您和每個人都知道。但話雖如此，正如我們之前所說，我們確實預計在 2022 年下半年將這種藥物帶給患者。

On the question on ulcerative colitis. You are right in the sense that the dose required in ulcerative colitis, Crohn's disease or IBD in general, is going to be 2x to 3x higher than what we see for psoriasis, and we've seen that for other molecules as well. And that is the intent of the ongoing trials to test out these doses. We obviously have not shared exactly what doses are being pursued for confidential reasons and competitive reasons. But we are looking at all avenues in terms of looking at the impact from not only PK but the PD outcomes as well. And we'll continue to follow those. And those will be the ways to define a proof of concept in this disease for pursuing further in ulcerative colitis.

關於潰瘍性結腸炎的問題。從某種意義上說，你是對的，潰瘍性結腸炎、克羅恩病或一般炎症性腸病所需的劑量將比牛皮癬所需的劑量高 2 至 3 倍，而且我們也發現其他分子也是如此。這就是正在進行的試驗的目的，以測試這些劑量。出於保密原因和競爭原因，我們顯然沒有確切地透露正在尋求的劑量。但我們正在考慮所有途徑，不僅考慮 PK 的影響，還考慮 PD 結果的影響。我們將繼續關注這些。這些將是定義這種疾病概念驗證的方法，以便進一步研究潰瘍性結腸炎。

In terms of the MK2, S1P1, BTK additional data, those trials are ongoing. As you know, these are in the Phase IIa, Phase IIb settings where we have multiple indications being pursued in BTK in the same trial in the autoimmune space. S1P1 also, additional work being done in Crohn's disease, for example, for Zeposia. And for MK2 as well, data is evolving. I can't say that you'll see the data in '22 or not, but certainly, we'll make it available as soon as we have evolution of the clinical outcomes for these data.

就MK2、S1P1、BTK附加數據而言，這些試驗正在進行中。如您所知，這些處於 IIa 期、IIb 期設置中，我們在自身免疫領域的同一試驗中在 BTK 中追求多種適應症。 S1P1 還針對克羅恩病開展了額外的工作，例如 Zeposia。對於 MK2 來說，數據也在不斷發展。我不能說您是否會在 22 年看到這些數據，但當然，一旦我們掌握了這些數據的臨床結果，我們就會立即提供這些數據。

Yes, we'll take our next question. from Chris Schott with JPMorgan.

是的，我們將回答下一個問題。來自摩根大通的克里斯·肖特 (Chris Schott)。

Just 2 questions for me. Maybe first, there seems to be a lot of debate on the rate of Revlimid erosion in '22. And I know you're not giving guidance for next year, but just any color you can provide there, both U.S. and international dynamics? And maybe specifically on the international side of the business, is it reasonable to think about the business as down like 50% for next year given the LOEs you're facing? Or are you thinking of something much better or worse than that? Just to get what you think that -- I think all have eroding over time, but just any color on the rate of erosion would be much appreciated.

只需問我 2 個問題。也許首先，關於來那度胺（Revlimid）在 22 年的侵蝕速度似乎存在很多爭論。我知道您不會提供明年的指導，但您可以提供任何顏色，包括美國和國際動態？也許特別是在業務的國際方面，考慮到您面臨的 LOE，認為明年業務下降 ​​50% 是否合理？或者你在想比這更好或更壞的事情嗎？只是為了得到你的想法——我認為隨著時間的推移，所有的東西都會被侵蝕，但只要任何關於侵蝕率的顏色都會非常感激。

And then the second question is a bigger picture one. You've been steadily rebuilding the portfolio here, but you've had a stock that's underperformed this year. And I think the Street remains concerned on some of these longer-term LOEs. Does that at some point lead to, I guess, a more aggressive deployment of your capital, whether that's a step-up in BD, you look at larger -- maybe later-stage deals or even going the other direction with more aggressive share repo? I'm just trying to get a sense of when you look at what, I think, you would think of as a disconnect between what's fundamentally happened with your business and the stock price, like how do you kind of think about starting to address that?

第二個問題是一個更大的問題。您一直在穩步重建投資組合，但您的股票今年表現不佳。我認為華爾街仍然對其中一些長期的 LOE 感到擔憂。我想，這是否會在某個時候導致你更積極地部署你的資本，無論是 BD 的升級，你會考慮更大的——也許是後期交易，甚至是通過更積極的股票回購走向另一個方向？我只是想了解一下，當你看到你的業務根本上發生的事情與股價之間的脫節時，我認為你會想到什麼，比如你如何考慮開始解決這個問題？

Thank you, Chris. Let me take your questions here. Giovanni. So first of all, on Revlimid generic entries, nothing has changed there. And let me just reiterate what we've said before and what we see happening next year. So next year, we will begin to see a volume limited generic competition in the U.S. And at the same time, we expect to see generic entries for Revlimid ex-U.S. That's consistent with what has always been our understanding. It has not changed. It's been fairly clear in our filings, and we're preparing for that.

謝謝你，克里斯。讓我在這裡回答你的問題。喬瓦尼.首先，Revlimid 仿製藥條目沒有任何變化。讓我重申一下我們之前說過的話以及我們預計明年會發生什麼。因此，明年，我們將開始在美國看到數量有限的仿製藥競爭，同時，我們預計將看到 Revlimid 在美國以外的仿製藥上市。這與我們一直以來的理解是一致的。它沒有改變。我們的文件中已經相當清楚地表明了這一點，我們正在為此做好準備。

The second thing that I would like to say is that if you remember, beginning at JPMorgan, we clearly articulated how we think about the company during the period of loss of exclusivity for Revlimid and Pomalyst. And we expect to be able to grow the company. In fact, we've articulated low to mid-single digit for the total company and low double digits for our continuing business through 2025. And when we provided that perspective, we obviously were reflecting our understanding of the Revlimid erosion.

我想說的第二件事是，如果你還記得的話，從摩根大通開始，我們就清楚地闡明了在 Revlimid 和 Pomalyst 失去獨家經營權期間我們對公司的看法。我們期望能夠發展公司。事實上，我們已經明確表示，到 2025 年，整個公司的業務將保持在低至中個位數的水平，而我們的持續業務將保持在低兩位數的水平。當我們提供這一觀點時，我們顯然是在反映我們對 Revlimid 侵蝕的理解。

And I think the conviction that we have that we can continue to grow the company is really driven by the belief which is proving right, that the combination of strong growth from our inline products, and namely Opdivo and Eliquis, combined with the strong uptake of our launch brands, which is happening, would more than offset the loss of exclusivity of Revlimid internationally next year and then over time in the U.S. So while I'm not going to give you exactly a percentage of erosion for next year. And we definitely will have an opportunity to talk more about this when we eventually provide guidance for the year. What I can tell you is that our belief remains strong. And I think that our perspective that we are able to grow sales and earnings per share applies to next year as well. And so nothing has really changed there.

我認為我們能夠繼續發展公司的信念實際上是由事實證明是正確的信念所驅動的，即我們的內嵌產品（即 Opdivo 和 Eliquis）的強勁增長與對我們正在推出的品牌將足以抵消來那度胺明年在國際上以及隨著時間的推移在美國失去的獨家經營權的損失。因此，雖然我不會向您提供明年的確切侵蝕百分比。當我們最終提供今年的指導時，我們肯定會有機會更多地討論這個問題。我可以告訴你的是，我們的信念依然堅定。我認為我們能夠增加銷售額和每股收益的觀點也適用於明年。所以那裡沒有任何真正的改變。

Now with respect to your second question that speaks to what are our priorities as we renew the portfolio in the face of LOEs. First of all, I think we have a rapidly evolving portfolio of new medicines that has tremendous potential, where we are executing multiple launches well. And I think our priority is always going to be, first, to maximize the opportunities that we have in a very, very rich late-stage pipeline. At the same time, we have tremendous financial flexibility, as David said. And obviously, we've seen -- we've said for some time now that business development is a priority for us as we think about allocating capital, and that continues to be the case.

現在，關於你的第二個問題，它涉及我們面對 LOE 更新投資組合時的優先事項。首先，我認為我們擁有快速發展的新藥組合，具有巨大潛力，並且我們正在很好地執行多次上市。我認為我們的首要任務始終是，首先，最大限度地利用我們在非常非常豐富的後期管道中擁有的機會。與此同時，正如大衛所說，我們擁有巨大的財務靈活性。顯然，我們已經看到——我們已經說過一段時間了，當我們考慮分配資本時，業務發展是我們的首要任務，而且情況仍然如此。

At the same time, as I've said before, we will be disciplined as we think about BD because we do have many opportunities to deploy our capital to accelerate growth. And I also believe that our capital allocation strategy will continue to be balanced where, as David mentioned, we have a history to look at our dividend, and we have increased our dividend consistently over the last several years. We've done that double digit in the last couple of years. And looking at share repurchases, year-to-date, we've repurchased $3.5 billion. We have an existing authorization for another $3 billion this year. And obviously, we'll continue to look at that as well.

與此同時，正如我之前所說，我們在考慮 BD 時會遵守紀律，因為我們確實有很多機會部署我們的資本來加速增長。我還相信，我們的資本配置策略將繼續保持平衡，正如大衛提到的，我們有查看股息的歷史，並且我們在過去幾年中持續增加了股息。過去幾年我們已經實現了兩位數的增長。從股票回購來看，今年迄今為止，我們已經回購了 35 億美元。今年我們已獲得另外 30 億美元的授權。顯然，我們也會繼續關注這一點。

But I can tell you that, of course, I understand the focus on LOEs at the same time, as we believe that we are executing really well on a plan to renew our portfolio, and we have tremendous financial flexibility to continue to make the right moves to do that.

但我可以告訴你，我當然理解對 LOE 的關注，因為我們相信我們在更新投資組合的計劃上執行得非常好，並且我們擁有巨大的財務靈活性來繼續做出正確的決定採取行動來做到這一點。

Next question is from Tim Anderson with Wolfe Research.

下一個問題來自沃爾夫研究公司的蒂姆·安德森。

A couple of questions. LAG-3, when can we expect that you'll have overall survival data on hand in melanoma for the package you've already submitted? And can you update us on what the development program looks like from here in terms of new trials and new tumor types? If I look at Roche with TIGIT, they pushed into lots of registrational trials, into lots of different tumors, kind of all at once. And I'm wondering why we're not seeing Bristol do the same here? Is it a signal that your confidence just isn't there yet in this molecule and that the survival data in melanoma is a gating factor?

有幾個問題。 LAG-3，我們什麼時候可以收到您已提交的包裹的黑色素瘤總體生存數據？您能否向我們介紹一下新試驗和新腫瘤類型方面的開發計劃的最新情況？如果我看看羅氏和 TIGIT，他們會同時進行大量註冊試驗，針對許多不同的腫瘤。我想知道為什麼我們沒有看到布里斯托爾在這裡做同樣的事情？這是否表明您對這種分子還沒有信心，並且黑色素瘤的生存數據是一個門控因素？

And then second question on mavacamten. Last quarter, I asked a question why you got only a standard review when it was awarded breakthrough therapy designation previously, I didn't quite understand your answer. But in 2019, it was pretty clear you expected a 2021 approval and launch. So I'm going to reask it here, are you confident you have an approvable drug at the PDUFA date? Or is there a potential that they'll want additional data and you'll get a CRL?

然後是關於 mavacamten 的第二個問題。上個季度，我問了一個問題，為什麼之前獲得突破性治療指定時你們只得到了標準審查，我不太明白你的答案。但在 2019 年，很明顯您預計 2021 年獲得批准並推出。所以我要在這裡重新問一下，您是否有信心在 PDUFA 日期擁有可批准的藥物？或者他們是否有可能需要更多數據並且您會獲得 CRL？

Sure. Thank you, Tim. Let me ask Samit to answer both of your questions, LAG-3 and mavacamten.

當然。謝謝你，蒂姆。讓我請 Samit 回答您的兩個問題：LAG-3 和 mavacamten。

Sure. Tim, for LAG-3, overall survival data, of course, is dependent on the events, and we are going to continue to follow them, and we'll share the data once available through our medical conference, but certainly make you aware of it. We have to remember, though, that in I-O therapies, more important than those hazard ratios are going to be the shape of the curve, and we're going to continue to watch out for that. and we'll share that when that becomes available. I cannot tell you exactly what the timing would be at this time.

當然。 Tim，對於 LAG-3，總體生存數據當然取決於事件，我們將繼續跟踪它們，一旦獲得數據，我們將通過我們的醫學會議分享，但肯定會讓您意識到它。但我們必須記住，在 I-O 療法中，比這些風險比更重要的是曲線的形狀，我們將繼續關注這一點。當可用時我們將分享它。我目前無法準確告訴您具體時間。

From a development program perspective, yes, the first aligned melanoma study read out, we submitted it. We have a PDUFA date for March of 2022. We have initiated the adjuvant trial in melanoma at this time. We have a randomized Phase II study ongoing in non-small cell lung cancer and plans to initiate Phase III trials late this year or meaning at the end of this year or early next year. And we have a randomized trial ongoing in hepatocellular carcinoma as a proof-of-concept generation.

從開發計劃的角度來看，是的，第一個一致的黑色素瘤研究讀出了，我們提交了它。我們的 PDUFA 日期為 2022 年 3 月。我們此時已啟動黑色素瘤的輔助試驗。我們正在進行一項針對非小細胞肺癌的隨機 II 期研究，併計劃在今年年底或今年年底或明年初啟動 III 期試驗。我們正在進行一項針對肝細胞癌的隨機試驗，作為概念驗證。

LAG-3, as you know, has had a history for a long time where we didn't have any data. So one has to ensure that the proof-of-concepts that we are following are going to be strong. And we believe that the trials that we have ongoing will give us that data to go forward. For TIGIT, if you recall, there is a proof-of-concept in non-small cell lung cancer, and that is a different tumor type and different milieu in terms of the tumor microenvironment. So we have to sort of judge the scientific data and put that in that perspective as we look for new tumor types to explore. And we'll certainly keep you posted as new tumor types are added in the LAG-3 program as well.

如您所知，LAG-3 已經有很長一段時間了，我們沒有任何數據。因此，我們必須確保我們遵循的概念驗證是強有力的。我們相信，我們正在進行的試驗將為我們提供前進所需的數據。對於 TIGIT，如果您還記得的話，非小細胞肺癌有一個概念驗證，那就是不同的腫瘤類型和不同的腫瘤微環境環境。因此，當我們尋找新的腫瘤類型來探索時，我們必須對科學數據進行某種判斷並從這個角度出發。隨著 LAG-3 計劃中添加新的腫瘤類型，我們一定會及時通知您。

For mavacamten, we are certainly comfortable with the data that we have from the EXPLORER trial from the efficacy perspective as well as safety perspective. We have a PDUFA date for January of next year. We have not heard from the FDA in terms of what additional data would be required. We certainly don't comment as to what the outcomes will be and how the ultimate decisions will be made by the agency, but we continue to engage with them. And as is usual for any filing, the back and forth in answering questions continues, but that is not unusual as we look at mavacamten or any of the drug.

對於 mavacamten，從功效和安全性角度來看，我們當然對 EXPLORER 試驗的數據感到滿意。我們確定 PDUFA 日期為明年 1 月。我們還沒有收到 FDA 的關於需要哪些額外數據的消息。我們當然不會評論結果是什麼以及該機構將如何做出最終決定，但我們將繼續與他們接觸。與任何申請一樣，反復回答問題仍在繼續，但當我們研究 mavacamten 或任何藥物時，這並不罕見。

We'll take our next question from Luisa Hector with Berenberg.

我們將回答 Luisa Hector 和 Berenberg 提出的下一個問題。

I wanted to check on deucravacitinib, whether you have started hiring your dermatology sales force already or whether this is -- so now that the Q4 and the reason for the phasing of the marketing cost into Q4 from Q3? And maybe you could also update us on where you are with your cost savings or where you plan to be by the end of this year? And what kind of increment we could see in 2022 [deucravacitinib] generic impact as well, just to think about the phasing of those various items?

我想檢查一下 deucravacitinib，你們是否已經開始招聘皮膚科銷售人員，或者是否是 - 那麼現在第四季度以及將營銷成本從第三季度分階段進入第四季度的原因？也許您還可以向我們介紹一下您的成本節省情況或您計劃在今年年底達到什麼水平？考慮一下這些不同項目的分階段，我們在 2022 年還可以看到 [deucravacitinib] 仿製藥的影響有什麼樣的增量？

So let's start with deucrava commercial investment in preparation of launch, Chris and then David, on synergies.

因此，讓我們從 deucrava 商業投資開始，準備發布，克里斯，然後是大衛，關於協同效應。

Sure. Thanks for the question. We are well on our way to building out the U.S. commercial and medical teams and feel great about the quality of the team that we're pulling together as well as the commercial readiness. The medical teams have actually been in place for a number of months. We've managed to hire a very strong team with deep dermatology experience there, key in-office roles have been filled and they're in the process of executing against launch plans, and we are building out the sales teams now.

當然。謝謝你的提問。我們在建設美國商業和醫療團隊方面進展順利，並對我們正在組建的團隊的質量以及商業準備情況感到非常滿意。醫療隊實際上已經到位好幾個月了。我們已經成功聘請了一支非常強大的團隊，擁有豐富的皮膚病學經驗，關鍵的辦公室職位已經填補，他們正在執行發布計劃，我們現在正在組建銷售團隊。

David?

大衛？

Great. And thanks for the question on synergies. The execution on the integration continues to go extremely well. As we indicated before, we'll overdeliver our initial commitment. We're now at $3 billion. By the end of this year, we anticipate being about $2.5 billion, which you may recall was the original overall commitment. So as we head into next year, getting to that $3 billion is what we're targeting. So good execution and continued overachievement of our initial expectations on the synergies.

偉大的。感謝您提出有關協同效應的問題。整合的執行繼續進展順利。正如我們之前指出的，我們將超額兌現我們最初的承諾。我們現在的資產是 30 億美元。到今年年底，我們預計約為 25 億美元，您可能還記得這是最初的總體承諾。因此，當我們進入明年時，我們的目標是達到 30 億美元。如此良好的執行力並持續超額實現我們對協同效應的最初預期。

Your next question will come from Andrew Baum with Citi.

您的下一個問題將來自花旗銀行的安德魯·鮑姆 (Andrew Baum)。

First question is on the TYK2. Number one, could you just update us on the additional maturing data sets in terms of what you're seeing from zoster, cardiovascular as well as a malignancy, if anything? And also, perhaps you could comment on in light of the recent FDA comments for JAKs in RA. How are you thinking about potential labeling for TYK2? Obviously, there's a [continuum of] potential label, some very unfavorable, some obviously more favorable.

第一個問題是關於TYK2的。第一，您能否向我們介紹一下您從帶狀皰疹、心血管疾病以及惡性腫瘤（如果有的話）中看到的其他成熟數據集的最新情況？另外，也許您可以根據 FDA 最近對 JAK 在 RA 中的評論發表評論。您如何看待 TYK2 的潛在標籤？顯然，存在一系列潛在的標籤，有些非常不利，有些顯然更有利。

And then second is in relation to your analyst meeting that is coming up, to what extent would you be able to talk to your Phase III program for your Factor XIa inhibitor? Or will we have to wait until you have the arterial data in hand next year before you and your partner can talk to the overall Phase III trial program?

其次是關於即將召開的分析師會議，您能在多大程度上談論您的 XIa 因子抑製劑的 III 期項目？或者我們是否必須等到您明年掌握動脈數據後，您和您的合作夥伴才能討論整個 III 期試驗計劃？

Sure, Andrew. Let me just start by giving you perspective about the investor meeting. And then we'll ask Samit to comment on the TYK2 program. So as we think about getting together in the middle of November, the objective is really primarily to give you an update on everything that has happened in the company and our portfolio over the last 2 years. It will be 2 years since we closed the acquisition of Celgene and a lot has happened. And so we'll talk about the progress with the pipeline, some of them is stage programs, the commercial opportunities we see from the asset, and we'll talk about the outlook for the company.

當然，安德魯。首先讓我向您介紹一下投資者會議的看法。然後我們將請 Samit 對 TYK2 計劃發表評論。因此，當我們考慮在 11 月中旬聚會時，我們的主要目標實際上是向您提供過去 2 年中公司和我們的投資組合所發生的一切最新情況。距離我們完成對 Celgene 的收購已經過去兩年了，發生了很多事情。因此，我們將討論管道的進展，其中一些是階段性計劃，我們從資產中看到的商業機會，我們將討論公司的前景。

Specifically, there will be an opportunity to focus on a few of those. So for example, as you know, the Milvexian data will be presented at AHA just before our meeting, and we look forward to discussing that update with you.

具體來說，將有機會重點關注其中的一些內容。例如，如您所知，Milvexian 數據將在我們會議之前在 AHA 上發布，我們期待與您討論該更新。

We're also making progress in another area, which is hematology, and that includes the CELMoDs and the Breyanzi second-line data that were mentioned earlier. They are expected to be at ASH, and we have an opportunity to review those at the event. So these are just some of the examples of the updates that we're planning on discussing at the meeting, and that includes some of the data sets that you were referencing. Samit?

我們還在另一個領域取得了進展，即血液學，其中包括前面提到的 CELMoD 和 Breyanzi 二線數據。他們預計將參加 ASH，我們有機會在活動中回顧他們。這些只是我們計劃在會議上討論的更新的一些示例，其中包括您引用的一些數據集。薩米特？

Yes. Thank you. And in regards to the TYK2 inhibitor, the long-term data that we continue to follow these patients and we've seen -- we don't see the profile differentiating in any other way than what we've already disclosed before. But we believe this is a TYK2 inhibitor not having a JAK-like signature. The overall profile from the lab parameters perspective, cardiovascular perspective, infection perspective remains stable as the data had been shared before. So we are looking forward to continuing the engagement with the agencies as we go forward and looking to bring it to patients in the second half of next year.

是的。謝謝。至於 TYK2 抑製劑，我們繼續跟踪這些患者的長期數據，我們已經看到——我們沒有看到與我們之前已經披露的情況相比有任何其他差異。但我們相信這是一種 TYK2 抑製劑，不具有類似 JAK 的特徵。從實驗室參數角度、心血管角度、感染角度來看，總體概況保持穩定，因為數據之前已共享。因此，我們期待在前進的過程中繼續與這些機構合作，並希望在明年下半年將其帶給患者。

As far as the JAK and labeling in RA as well as other conditions are concerned, again, these are going to be in the future as we go into discussions with the regulatory agencies how we see it. We don't see it as a JAK inhibitor, so we are not really thinking about it like that. We'll continue to update you once we get a more sound plays in terms of advice if there is any to be shared.

就 JAK 和 RA 中的標籤以及其他條件而言，這些都將在未來與監管機構討論我們如何看待它。我們不認為它是一種 JAK 抑製劑，所以我們並沒有真正這樣考慮它。一旦我們收到更多建議方面的聲音（如果有任何可以分享的內容），我們將繼續向您更新。

We'll take our next question from Carter Gould with Barclays.

我們將回答巴克萊銀行卡特·古爾德的下一個問題。

First, I guess, maybe start with commercial. I wanted -- hoping you could add maybe a little bit more in terms of anything tangible on sort of UC demand with Zeposia and to what extent the start of the year will be sort of an important milestone in terms of broadening access? And then maybe just a clarifying question on deucravacitinib. Samit, you talked about in UC needing to explore doses 2x to 3x higher than what's active in psoriasis. I know you don't want to get into specific doses, but are you exploring something above and beyond sort of the 12 mg that I think was the high end in the psoriasis study? And then I know it's a bit of a sensitive topic given some of the ongoing litigation, but just maybe how you're thinking about sort of the backup TYK2 compounds you have in your portfolio?

首先，我想，也許可以從商業廣告開始。我希望——希望您能在 Zeposia 的 UC 需求方面添加更多具體內容，以及今年年初在擴大訪問方面將在多大程度上成為一個重要的里程碑？然後也許只是一個關於 deucravacitinib 的澄清問題。 Samit，您談到在 UC 中需要探索比銀屑病有效劑量高 2 到 3 倍的劑量。我知道您不想進入特定劑量，但您是否正在探索 12 毫克（我認為是銀屑病研究的高端劑量）以外的藥物？然後我知道考慮到一些正在進行的訴訟，這是一個有點敏感的話題，但也許您如何考慮您的投資組合中的備用 TYK2 化合物？

Sure. Chris, why don't you start on UC demand?

當然。克里斯，你為什麼不開始滿足 UC 的需求呢？

Yes. So we feel very good about the performance that we're seeing for Zeposia in UC. And let me start with execution. The execution of the team really since approval has been very strong. We've got very good awareness for the product. The unaided awareness now is over 60%, aided awareness is well over 90%. Since approval in UC, we estimate that we have around 400 trialists that have already begun to utilize the product, virtually all of the gastros that we surveyed were aware of Zeposia or interested in trying it. And frankly, in spite of still relatively restricted access environment, the sales teams are having very good success in engaging with customers, both in person and remotely. So from an execution standpoint, it's early days but we feel very good about where we are.

是的。因此，我們對 Zeposia 在 UC 中的表現感到非常滿意。讓我從執行開始。自從獲得批准以來，團隊的執行力確實非常強。我們對產品有很好的認識。目前無輔助意識已超過 60%，輔助意識遠超過 90%。自 UC 獲得批准以來，我們估計大約有 400 名試用者已經開始使用該產品，幾乎所有我們調查的胃病患者都知道 Zeposia 或有興趣嘗試它。坦率地說，儘管訪問環境仍然相對受限，但銷售團隊在與客戶面對面和遠程接觸方面取得了非常好的成功。因此，從執行的角度來看，現在還處於早期階段，但我們對目前的情況感覺非常好。

As you note, access is going to be -- continue to be something we pay a lot of attention to. We feel good about our ability to start generating volume this year and into the first part of next year, and we think that volume will build momentum as we get into the second half of 2022 when we begin to get additional more favorable access with key payers. But so far, the UC performance that we're seeing commercially is very, very strong and very happy with where we sit.

正如您所指出的，訪問將繼續成為我們非常關注的事情。我們對今年和明年上半年開始產生銷量的能力感到滿意，並且我們認為，隨著我們進入 2022 年下半年，屆時我們開始與主要付款人獲得更多更優惠的准入，銷量將會增強勢頭。但到目前為止，我們在商業上看到的 UC 性能非常非常強勁，並且對我們所處的位置非常滿意。

Thank you, Chris. Before I ask Samit to comment on the deucrava dose, let me just say, Carter, we're not going to comment on any ongoing litigation. I just want to say that, that litigation is really not related at all to the BMS program or any backup that may exist. So they're completely different programs, and there is no relationship there.

謝謝你，克里斯。在我請薩米特對德克拉瓦劑量發表評論之前，我只想說，卡特，我們不會對任何正在進行的訴訟發表評論。我只是想說，該訴訟實際上與 BMS 程序或任何可能存在的備份無關。所以它們是完全不同的程序，並且沒有任何關係。

Yes. And just a minor thing to add over here is, as we talk about the doses without getting into the specifics of it, I can tell you that we selected the doses which are higher than what we used in the psoriasis program based on PK modeling. And taking into account the historical experience, we will certainly say that at this point, we don't know if these higher doses will translate into efficacy or not. That's the proof of concept we're trying to get. And once that is available, that will certainly pave the way for the future program. We will need to see what the data are from the next trials that we are pursuing right now, both in Crohn's disease as well as in ulcerative colitis.

是的。這裡需要補充的一點是，當我們談論劑量而不深入具體細節時，我可以告訴您，我們選擇的劑量高於基於 PK 模型的銀屑病項目中使用的劑量。考慮到歷史經驗，我們肯定會說，在這一點上，我們不知道這些更高的劑量是否會轉化為療效。這就是我們想要得到的概念證明。一旦可用，這肯定會為未來的計劃鋪平道路。我們需要了解我們目前正在進行的下一項試驗的數據，包括克羅恩病和潰瘍性結腸炎。

We'll take our next question from Ronny Gal with Bernstein.

我們將回答 Ronny Gal 和 Bernstein 提出的下一個問題。

The first one is on the PD-1 space. There's been some debate about the approvability of follow-on PD-1 with data from Asian populations only. You've obviously generated a lot of data in various populations. And I was wondering if there was any scientific basis to this concern that is in your trials, is there a difference in either efficacy or safety in different ethnic populations with your PD-1?

第一個是 PD-1 空間。對於僅來自亞洲人群的數據的後續 PD-1 的批准性存在一些爭論。顯然，您已經在不同人群中生成了大量數據。我想知道您的試驗中的這種擔憂是否有任何科學依據，您的 PD-1 在不同種族人群中的療效或安全性是否存在差異？

And second, on Washington and the discussion around price reform in the drug area, it seems to be clear that the negative scenario, so the industry will not play out. But there is still some discussion of pharma contributing to catastrophic insurance in Part D. And if there will be price negotiations, the discussions seem to be focused on Part B as in boy. Given that you're essentially more exposed to the oncology space, I was wondering if this -- if there's any basis for that? Is there a risk that oncology will take the brunt of the impact of the [DC or whatever give a way to take in]? Or will it be more balanced across product types?

其次，關於華盛頓和圍繞藥品領域價格改革的討論，似乎很明顯負面情景，因此該行業不會發揮作用。但在 D 部分中，仍有一些關於製藥公司為巨災保險做出貢獻的討論。如果要進行價格談判，討論似乎會集中在 B 部分，就像《男孩》中一樣。鑑於您本質上更多地接觸腫瘤學領域，我想知道這是否有任何基礎？腫瘤學是否有可能首當其沖地受到[DC或任何提供吸收途徑]影響的風險？還是跨產品類型會更加平衡？

Thanks, Ronny. Let me just start there, and then I'll ask Samit to comment on your question about PD-1 development. So let me just start by saying that it's really difficult to forecast at this point what price reform may look like in the future. From my perspective, what's important is that any change that is made actually improves affordability of medicines for patients. And that's the lens that we are applying. And from that perspective, there are a number of elements of potential reform like establishing out-of-pocket caps in Part D, redesign of the Part D's benefit to reduce the exposure of patients that we support, and we also support some changes like introducing market forces in Part B.

謝謝，羅尼。讓我從這裡開始，然後我將請 Samit 評論一下您關於 PD-1 開發的問題。首先我要說的是，目前還很難預測未來的價格改革會是什麼樣子。在我看來，重要的是所做的任何改變實際上都會提高患者的藥物負擔能力。這就是我們正在應用的鏡頭。從這個角度來看，潛在的改革有許多要素，例如在 D 部分中設立自付費用上限，重新設計 D 部分的福利以減少我們支持的患者的暴露，我們還支持一些改變，例如引入B 部分中的市場力量。

Very difficult to answer your question with respect to whether a disproportionate impact may happen in oncology or not. I think what's important is that we don't go to reforms that actually impact the ability of the industry overall to continue to invest in innovation. And that's the primary lens here.

很難回答你關於腫瘤學是否會發生不成比例的影響的問題。我認為重要的是，我們不會進行真正影響整個行業繼續投資創新能力的改革。這就是這裡的主要鏡頭。

I think from the perspective of the BMS portfolio, when you look at our portfolio, it's actually very diversified across therapeutic areas, across actually Part B versus Part D. And so I can't speculate what the impact of any reform would be on us. I think what's really important is to continue to advocate for reforms that yes, improve affordability of medicines for patients, but at the same time, enable us to continue to invest in innovation. And some of the hyperpartisan scenarios being discussed in Washington would actually impact both negatively.

我認為從 BMS 投資組合的角度來看，當你看我們的投資組合時，它實際上在治療領域非常多元化，實際上是 B 部分與 D 部分。所以我無法推測任何改革會對我們產生什麼影響。我認為真正重要的是繼續倡導改革，是的，提高患者的藥品負擔能力，但同時使我們能夠繼續投資於創新。華盛頓正在討論的一些極端黨派情景實際上會對兩者產生負面影響。

Yes. And just starting from where you left off in terms of the portfolio, we have a very broad portfolio, which means that when we conduct our clinical trials, we do them globally, including those in the Asian countries. And when we file the data, we have to provide subset analysis by region or sometimes even by country, and that's how we seek approval in some of the regions and countries of the world, including in Asia. As it comes to the PD-1 inhibitors, where we have conducted clinical trials globally and across the 20-odd indications or 12-plus tumor types that have now sought approvals, we don't see a major difference occurring because of regional differences or population differences. That doesn't mean that representation of larger populations may not be required in clinical trials. So one has to just keep that in mind rather than thinking about a singular country trial will lead to approvals or not.

是的。從您上次提到的產品組合開始，我們擁有非常廣泛的產品組合，這意味著當我們進行臨床試驗時，我們會在全球範圍內進行，包括在亞洲國家進行。當我們提交數據時，我們必須按地區甚至有時甚至按國家提供子集分析，這就是我們尋求世界上一些地區和國家（包括亞洲）批准的方式。就 PD-1 抑製劑而言，我們已經在全球範圍內針對 20 多種適應症或 12 多種腫瘤類型進行了臨床試驗，目前已尋求批准，我們認為不會因為地區差異或差異而出現重大差異。人口差異。這並不意味著臨床試驗中可能不需要更多人群的代表。因此，人們必須牢記這一點，而不是考慮單一國家的試驗是否會獲得批准。

We'll take our next question from Matthew Harrison with Morgan Stanley.

我們將接受摩根士丹利的馬修·哈里森提出的下一個問題。

Great. I guess 2 for me. So first, on the second-line CAR T study. I'm just wondering how you're thinking about that commercially. And specifically, whether you think you need longer-term follow-up to compare to transplant for that to be commercially successful. And then as we look at the data coming at ASH, I think we're going to get data from Kite's study as well. I'm wondering if there's any differentiation you're looking for your product versus those?

偉大的。我猜對我來說是2。首先是二線CAR T研究。我只是想知道你在商業上是如何看待這個問題的。具體來說，您是否認為需要與移植進行更長期的隨訪才能獲得商業上的成功。然後，當我們查看 ASH 的數據時，我認為我們也將從 Kite 的研究中獲取數據。我想知道您正在尋找的產品與其他產品相比是否有任何區別？

And then second on Zeposia. I'm just wondering if you could talk about or you thought about if Biogen wins their appeal on Tecfidera and branded Tecfidera comes back to the market, does that change any of your assumptions and how you think about the MS market?

然後是 Zeposia。我只是想知道您是否可以談談或者您想過如果百健（Biogen）贏得了對 Tecfidera 的上訴並且 Tecfidera 品牌重返市場，這是否會改變您的任何假設以及您對 MS 市場的看法？

Thank you. Thanks, Matthew. Let me start with Chris, just maybe a comment on Zeposia. And then we can move to the second-line CAR T data and Samit will add some comments.

謝謝。謝謝，馬修。讓我從 Chris 開始，也許只是對 Zeposia 的評論。然後我們可以轉向二線 CAR T 數據，Samit 會添加一些評論。

Yes. So just on Zeposia very quickly, we have -- we don't anticipate that any potential change on the Tecfidera side would have an impact on us. We've seen very limited competitive impact of generic Tecfidera that's prominently been cannibalization of branded Tec and then obviously a shift in the utilization within that portfolio. Our focus on Zeposia in the MS side continues to be not only establishing ourselves as the #1 SP, which we are right now in terms of written scripts, but also becoming the #1 oral. And so our focus will continue to be, in a very disciplined way, focused on that.

是的。因此，很快就 Zeposia 而言，我們預計 Tecfidera 方面的任何潛在變化不會對我們產生影響。我們看到仿製藥 Tecfidera 的競爭影響非常有限，主要是品牌 Tec 的蠶食，然後是該產品組合中利用率的明顯轉變。我們對 MS 方面 Zeposia 的關注不僅是確立我們目前在書面腳本方面排名第一的 SP，而且還成為口頭排名第一的 SP。因此，我們的重點將繼續以非常嚴格的方式集中於此。

And then let me just give the commercial perspective on the second-line CAR T study, and then I'll turn it over to Samit. When you look at that second line setting generally, you generally see that population diverting to those physicians who tend to be very focused on transplant. There's a sort of defined segment of those physicians. There are a number of physicians who are very open and look for opportunities to avoid transplant where possible. And then there are a number of physicians who really take it on a case-by-case basis. And so we're excited about the data that we've seen so far, and look forward to seeing that data continue to play out and be presented at ASH, and we'll adjust obviously accordingly from a commercial standpoint.

然後讓我簡單介紹一下二線 CAR T 研究的商業角度，然後我會將其交給 Samit。當您總體觀察二線環境時，您通常會發現人群轉向那些往往非常專注於移植的醫生。這些醫生中有一個明確的部分。有許多醫生非常開放，並尋找機會盡可能避免移植。還有一些醫生確實根據具體情況進行治療。因此，我們對迄今為止看到的數據感到興奮，並期待看到這些數據繼續發揮作用並在 ASH 上展示，我們將從商業角度進行相應的調整。

Yes. And just continuing that excitement from a data perspective, we truly are looking forward to sharing the data at ASH from the second-line study. And EFS in this particular case is accepted endpoint from a regulatory perspective. So looking forward to certainly getting engagement with the agency and getting this again to the patients as soon as possible.

是的。從數據角度繼續這種興奮，我們真誠地期待在 ASH 上分享二線研究的數據。從監管角度來看，在這種特殊情況下，EFS 是可接受的終點。因此，我們期待著與該機構的合作，並儘快將其再次提供給患者。

We'll obviously continue to follow patients for overall survival. And as is required for CAR T cell therapies, long-term safety follow-up as well. So those data will evolve and will be shared in the future. At the current time, the primary endpoint of the study was EFS, and we have that in hand, and that will be presented.

顯然，我們將繼續跟踪患者的總體生存情況。正如 CAR T 細胞療法所要求的那樣，還需要長期的安全性隨訪。因此，這些數據將會不斷發展並在未來共享。目前，該研究的主要終點是 EFS，我們已經掌握了該終點，並將予以介紹。

We'll take our next question from Steve Scala with Cowen.

我們將回答 Steve Scala 和 Cowen 提出的下一個問題。

A couple of questions. Lupus seems like an area of strategic interest to the company. Does Bristol feel it has all the assets it needs in lupus? Or would you look for M&A to supplement this area? So that's one question. Second question is on the Factor XIa data at AHA. It was mentioned on this call that the company is excited about what we are going to see. On the second quarter call, Samit, you noted that the data we're going to see is dose finding and safety data. So should we conclude that what we will see at AHA is that you have the Phase III dose and it is proven safe? Or might we see more than that?

有幾個問題。狼瘡似乎是該公司的戰略利益領域。布里斯托爾是否認為它擁有狼瘡所需的所有資產？或者您會尋求併購來補充這一領域嗎？這是一個問題。第二個問題是關於 AHA 的 XIa 因子數據。這次電話會議中提到，該公司對我們將要看到的情況感到興奮。在第二季度的電話會議上，薩米特，您指出我們將看到的數據是劑量發現和安全數據。那麼，我們是否應該得出這樣的結論：我們將在 AHA 看到的是，您擁有 III 期劑量並且已被證明是安全的？或者我們可能會看到更多？

Samit, do you want to take both?

薩米特，你想兩個都帶嗎？

Sure. Absolutely. Thank you, Steve, for your questions. And starting with lupus, as you know, that we will, first of all, get the data for deucravacitinib in SLE at the beginning of next year. We have a discoid lupus study that is also ongoing, which will read out in '23 or later part of that. We have a couple of other assets in early developments, which are on ClinicalTrials.gov, which we have ongoing studies looking at lupus as well. So we do believe that we've covered a broad range of targets and broad range of medicines being explored in lupus and one of those -- or several of those could be pursued for the future.

當然。絕對地。史蒂夫，謝謝你的提問。正如您所知，從狼瘡開始，我們首先將在明年初獲得 deucravacitinib 治療 SLE 的數據。我們還有一項正在進行中的盤狀狼瘡研究，該研究將於 23 年或稍後部分公佈。我們還有其他一些處於早期開發階段的資產，這些資產位於 ClinicalTrials.gov 上，我們也正在進行針對狼瘡的研究。因此，我們確實相信，我們已經涵蓋了正在探索的狼瘡治療的廣泛目標和廣泛藥物，其中一種或其中幾種可以在未來進行探索。

From an XIa perspective, for Milvexian, as we've said, at AHA, you'll see the data. And there are 2 things to really take away. One, the intent of the study was to define a range of dose that will be pursued for future evaluation in Phase III once the data from SSP study is also available. So that collective data set then leads to the decision-making for future exploration and indications as we go forward.

從 XIa 的角度來看，對於 Milvexian，正如我們所說，在 AHA，您會看到數據。有兩件事值得我們注意。第一，該研究的目的是確定一個劑量範圍，一旦獲得 SSP 研究的數據，將在 III 期臨床試驗中進行未來的評估。這樣，隨著我們的前進，集體數據集就會為未來的探索和指示做出決策。

Second, we wanted to see a differentiation in terms of not only efficacy, but very importantly, from a safety and bleeding risk perspective. And when we think about that, it is going to be important to pay attention to major bleeds and minor bleeds and overall bleeds. So those are the kinds of things that you probably will see at AHA and then we can certainly have a discussion in the middle of next month when we have the presentations for the investors meeting.

其次，我們不僅希望看到功效方面的差異，而且非常重要的是，從安全性和出血風險的角度來看。當我們想到這一點時，注意大出血、小出血和整體出血就很重要。這些是您可能會在 AHA 上看到的事情，然後我們當然可以在下個月中旬為投資者會議做演示時進行討論。

We'll take our next question from Dane Leone with Raymond James.

我們將回答戴恩·萊昂內和雷蒙德·詹姆斯提出的下一個問題。

Congratulations on the update. I'll keep it to 2 for me. Firstly, just going back to the generic erosion debate heading into 2022. Taking a different angle, obviously, post the acquisition of Celgene that was accretive to your overall operating margin, the question from a lot of us have followed. Celgene, historically, along with Bristol has been -- the belief was Revlimid drove a lot of that margin for Celgene. And with that going away, even with new brands ramping up, is there enough from the portfolio and steady state growth of maybe Eliquis and Opdivo to offset an impact operationally from EBITDA? Or will there need to be bridging, like you said, of additional cost efficiencies from the organization? So that's one, essentially getting to whether there could be a lost year or 2 of EBITDA growth from the existing portfolio.

恭喜更新。我會把它保留為2。首先，回到 2022 年關於通用侵蝕的爭論。顯然，從不同的角度來看，在收購新基 (Celgene) 後，這增加了你的整體運營利潤，我們很多人都提出了這個問題。從歷史上看，新基（Celgene）和布里斯托爾（Bristol）一直相信來那度胺（Revlimid）為新基（Celgene）帶來了很大的利潤。隨著這種情況的消失，即使新品牌不斷湧現，Eliquis 和 Opdivo 的產品組合和穩定增長是否足以抵消 EBITDA 帶來的運營影響？或者像您所說的那樣，是否需要為組織提供額外的成本效率？所以這就是一個問題，本質上是要確定現有投資組合是否會損失一年或兩年的 EBITDA 增長。

Secondly, a quick one for me. It's been brought up a lot why the team has not aggressively moved to start studies in more of a mild to moderate population for Zeposia in ulcerative colitis. So any thoughts around the development plan there would be appreciated.

其次，對我來說是一個快速的過程。人們多次提出為什麼該團隊沒有積極地在更多的輕度至中度人群中開展 Zeposia 治療潰瘍性結腸炎的研究。因此，任何有關發展計劃的想法都將受到讚賞。

Thanks very much. So let me just start and ask David to make some comments there. I'll just reiterate what I said earlier that from our perspective, as we think about the period of loss of exclusivity of Revlimid, first of all, we always said that our perspective of that, particularly in the U.S., there will be a slope that would be happening over time. We've made a comment in the past, we were more conservative on that slope than consensus. At the same time, we believe strongly in the fact that the growth of the inline portfolio and the launch brands will actually enable the company to grow through that period. But David can give you a better perspective about the profitability of our business going forward and how we think about that.

非常感謝。因此，讓我開始請大衛發表一些評論。我只是重申一下我之前所說的，從我們的角度來看，當我們考慮來那度胺失去獨占權的時期時，首先，我們總是說，我們對此的看法，特別是在美國，將會有一個斜率隨著時間的推移，這種情況將會發生。我們過去曾發表過評論，我們在這個坡度上比共識更加保守。與此同時，我們堅信，內聯產品組合和推出品牌的增長實際上將使公司能夠度過這一時期。但大衛可以讓您更好地了解我們業務未來的盈利能力以及我們對此的看法。

Yes. Thanks, Dane, for the question. And we feel very confident in our ability to maintain our operating margins in the low to mid-40% through 2025. And there's a couple of things driving that. One, as I discussed earlier, we're doing better on our synergies and strong execution against that as we head into next year and the run rate after that. I'd say the other is we've been very disciplined on the P&L side of things. And as you may note, from an MS&A perspective, we're very efficient and top tier in our industry. And the other thing I would say is that we've been very disciplined from the standpoint of reallocating resources from those LOE brands to our launch brands which gives us further confidence in that.

是的。謝謝丹恩提出的問題。我們對到 2025 年將營業利潤率維持在 40% 左右的水平非常有信心。有幾個因素推動了這一點。一，正如我之前討論的，隨著我們進入明年以及之後的運行率，我們在協同效應和強有力的執行方面做得更好。我想說的另一個是我們在損益方面一直非常自律。正如您可能注意到的，從管理與收購的角度來看，我們非常高效，並且在行業中處於領先地位。我要說的另一件事是，從將資源從那些 LOE 品牌重新分配到我們的推出品牌的角度來看，我們一直非常自律，這讓我們對此更有信心。

And the last thing is if you think about the portfolio and the launches, many of those products have strong margins, as you talked about on the inline with Opdivo being a high-margin product, but also some of the other ones that are in the launch portfolio like Zeposia as well as Reblozyl. Those products have nice margins as well. So that's what gives us confidence in our ability to keep those operating margins in that low to mid-40s as we progress.

最後一件事是，如果您考慮產品組合和發布，其中許多產品都有很高的利潤率，正如您在 Opdivo 中談到的那樣，它是一種高利潤率產品，但也有一些其他產品在推出 Zeposia 和 Reblozyl 等產品組合。這些產品也有不錯的利潤。因此，這讓我們相信，隨著我們的進步，我們有能力將營業利潤率保持在 40 左右的低水平。

And in terms of Zeposia, we have obviously got the indication for MS as well as UC and the trials are ongoing in Crohn's disease, we currently do not have any plans in the mild to moderate patients with UC at this time.

就 Zeposia 而言，我們顯然已經獲得了 MS 和 UC 的適應症，克羅恩病的試驗正在進行中，目前我們還沒有針對輕至中度 UC 患者的任何計劃。

We'll take our question from Matt Phipps with William Blair.

我們將回答馬特·菲普斯和威廉·布萊爾提出的問題。

You mentioned that Abecma would be relatively flat going into the fourth quarter. But should we expect to be more or less flat until the vector supply issue is resolved, which I think you said would occur in the second half of next year? And then can you just comment on if the higher dose that was explored in the LATTICE-UC trial with deucra is also being explored in Crohn's and SLE or just maybe how there's different doses amongst those indications as well?

您提到 Abecma 進入第四季度將相對持平。但是，在載體供應問題得到解決之前，我們是否應該期望或多或少持平？我認為您所說的問題將在明年下半年發生？然後您能否評論一下 LATTICE-UC 試驗中使用 deucra 探索的更高劑量是否也在克羅恩病和 SLE 中探索，或者這些適應症中是否也有不同的劑量？

Chris and then Samit.

克里斯，然後是薩米特。

So just quickly on Abecma. Yes, we've commented on how we anticipate Abecma sales growing in Q4. And we've also said that we are staying very focused on increasing vector supply as we get into the first half of next year. And so I don't have the ability to give you any additional information for next year. But obviously, we'll continue to update you on future calls.

因此，請快速使用 Abecma。是的，我們已經評論了我們對 Abecma 第四季度銷售額增長的預期。我們還說過，進入明年上半年，我們將非常專注於增加載體供應。因此，我無法向您提供明年的任何其他信息。但顯然，我們將在未來的電話會議中繼續向您通報最新情況。

Yes. And as it relates to the doses, again, on deucravacitinib in UC and CD, there are some similarities in the doses, but we have optionality over here to amend and change the dosing patterns here. So we'll continue to work with our DMC as well as our clinical trials teams are looking into the data to see if there are any adjustments needed for either of the 2 trials.

是的。由於與劑量相關，德克拉瓦西替尼治療 UC 和 CD 的劑量有一些相似之處，但我們可以選擇修改和改變劑量模式。因此，我們將繼續與 DMC 合作，我們的臨床試驗團隊正在研究數據，看看這兩項試驗是否需要進行任何調整。

Thanks, everyone. Thanks again for participating in the call. We had a great quarter with very, very strong performance. The launch portfolio continues to progress, inline brands are growing strongly. We look forward to the opportunity to continue to discuss the evolution of the pipeline and the future outlook of the company when we get together in the middle of November for our Investor Day. Tim and the rest of his team will be available throughout the day to answer any other questions you have. Thanks, and have a good day.

感謝大家。再次感謝您參與通話。我們度過了一個很棒的季度，表現非常非常強勁。推出的產品組合不斷進步，內聯品牌增長強勁。我們期待在 11 月中旬的投資者日聚會時有機會繼續討論產品線的演變和公司的未來前景。蒂姆和他的團隊的其他成員將全天回答您的任何其他問題。謝謝，祝你有美好的一天。

And this concludes today's call. Thank you for your participation. You may now disconnect.

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連接。